Tacrolimus concentration/dose ratio influences renal functions after liver transplantation

BACKGROUND: The calcineurin inhibitor (CNI) tacrolimus (Tac) is an effective immunosuppressant used after liver transplantation (LTx), but is often associated with CNI nephrotoxicity. Currently, there is no simple clinical predictor for CNI nephrotoxicity after LTx. We hypothesized that the Tac meta...

Authors: Thölking, Gerold Bernhard
Siats, Lea
Fortmann, Christian
Koch, Raphael
Hüsing, Anna Katharina Elisabeth Pia
Cicinnati, Vito R.
Gerth, Hans Ulrich
Wolters, Heiner
Anthoni, Christoph
Pavenstädt, Hermann
Suwelack, Barbara
Schmidt, Hartmut
Kabar, Iyad
Division/Institute:FB 05: Medizinische Fakultät
Document types:Article
Media types:Text
Publication date:2016
Date of publication on miami:25.05.2016
Modification date:23.01.2020
Edition statement:[Electronic ed.]
Source:Annals of Transplantation 21 (2016), 167-179
Subjects:Calcineurin; Liver Transplantation; Metabolism; renal insufficiency; Tacrolimus
DDC Subject:610: Medizin und Gesundheit
License:CC BY-NC-ND 4.0
Language:English
Notes:Finanziert durch den Open-Access-Publikationsfonds 2015/2016 der Westfälischen Wilhelms-Universität Münster (WWU Münster).
Format:PDF document
ISSN:2329-0358
URN:urn:nbn:de:hbz:6-65289635569
Permalink:http://nbn-resolving.de/urn:nbn:de:hbz:6-65289635569
Other Identifiers:DOI: 10.12659/AOT.895898
Digital documents:895898.pdf

BACKGROUND: The calcineurin inhibitor (CNI) tacrolimus (Tac) is an effective immunosuppressant used after liver transplantation (LTx), but is often associated with CNI nephrotoxicity. Currently, there is no simple clinical predictor for CNI nephrotoxicity after LTx. We hypothesized that the Tac metabolism rate – defined as the blood concentration normalized by its daily dose (the C/D ratio) – is associated with post-LTx renal impairment. MATERIAL AND METHODS: We analyzed the relationship between the C/D ratio and post-transplant renal function in 179 patients who underwent LTx between 2000 and 2012 and were initially immunosuppressed with Tac, mycophenolate mofetil, and prednisolone. Six months after LTx, 115 patients were categorized into 1 of 2 groups based on their Tac C/D ratio (<1.09 or ≥1.09): fast (n=58) or slow (n=57) metabolizers. The renal function was determined 36 months after LTx using the estimated glomerular filtration rate (eGFR) as described by Cockcroft and Gault. RESULTS: At the time of LTx there was no statistically significant difference between the eGFR of fast and slow metabolizers. Six months (P=0.016), 12 months (P=0.001), and 36 months (P=0.018) after LTx, fast Tac metabolizers had significantly more impaired renal function than slow metabolizers. Because of a presumption of CNI nephrotoxicity, 32.8% of fast metabolizers and 14.0% of slow metabolizers were switched from Tac to other immunosuppressants (P=0.027). CONCLUSIONS: In this study, the Tac metabolism rate appears to influence renal function after LTx, suggesting that a C/D ratio of <1.09 is associated with increased CNI nephrotoxicity in LTx recipients.